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Background

Obesity is among biggest risk factors in development of esophageal adenocarcinoma (EAC). Recent studies demonstrate that obese patients have metabolic changes that increase insulin-like growth factor-1 (IGF-1), free fatty acid (FFA), and diacylglycerol (DAG) levels. Alteration in IGF-1, FFA, and DAG regulates apoptotic gene expression though changes in FLIP and cIAP2. Hypothesis is to assess role of FLIP and cIAP2 in EAC.

Methods

Included 17 males with either Barrett’s Esophagus (BE) or EAC with or without BE. We collected normal, BE, and EAC tissue samples during endoscopy or esophagectomy. Seven were obese (average BMI= 34.0 kg/m2) and 10 were non-obese (average BMI= 24.90 kg/m2). Samples were analyzed for presence of pro-apoptotic, anti-apoptotic factors, cIAP2, FLIP, IGF-1, Akt, NF-kB and Ki67 expression levels by immunofluorescence and RT-PCR. We compared expression levels between Normal, BE, and EAC tissue.

Results

Showed increased gene and protein expression of cIAP2, FLIP, NF-kB, IGF-1, Akt, and Ki67 in BE and EAC samples compared to normal tissues. Correlation analysis of gene expression between nonobese and obese patients for IGF-1, cIAP2 and FLIP showed strong obesity correlation with IGF-1, cIAP2 and FLIP. Correlation coefficient for cIAP2 and FLIP was 0.5483 and 0.7811 for normal, 0.5602 and 0.8293 for BE, and 0.8266 and 0.7977 for EAC (Figure 1).

Conclusions

Obese patients with EAC had increased expression of cIAP2 and FLIP, which is associated with inhibition of apoptosis and possible progression of esophageal adenocarcinoma. These results need to be confirmed with future invitro studies with or without specific inhibitors.